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Title:
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Risk of acute liver injury in agomelatine and other antidepressant users in four european countries: a cohort and nested case–control study using automated health data sources
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Author:
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Pladevall-Vila, Manel; Pottegård, Anton; Schink, Tania; Reutfors, Johan; Morros, Rosa; Poblador-Plou, Beatriz; Timmer, Antje; Forns, Joan; Hellfritzsch, Maja; Reinders, Tammo; Hägg, David; Giner-Soriano, Maria; Prados-Torres, Alexandra; Cainzos-Achirica, Miguel; Hallas, Jesper; Brandt, Lena; Cortés, Jordi; Aguado, Jaume; Perlemuter, Gabriel; Falissard, Bruno; Castellsagué, Jordi; Jacquot, Emmanuelle; Deltour, Nicolas; Perez-Gutthann, Susana
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Other authors:
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[Pladevall-Vila M] RTI Health Solutions, Barcelona, Spain. The Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA. [Forns J, Castellsagué J, Cainzos-Achirica M, Aguado J, Perez-Gutthann S] RTI Health Solutions, Barcelona, Spain. [Pottegård A, Hellfritzsch M, Hallas J] Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark. [Schink T, Reinders T] Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany. [Reutfors J, Hägg D, Brandt L] Centre for Pharmacoepidemiology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. [Morros R, Giner-Soriano M, Cortés J] Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAPJGol), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Institut Català de la Salut, Barcelona, Spain. [Falissard B] CESP INSERM U1018, Université Paris-Saclay, Université Paris-Sud, UVSQ, APHP, Paris, France. [Poblador-Plou B, Prados-Torres A] EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Aragon, REDISSEC ISCIII, Miguel Servet University Hospital, Zaragoza, Spain. [Timmer A] Division of Epidemiology and Biometry, Medical Faculty, Carl von Ossietzky University, Oldenburg, Germany. [Perlemuter G] Service d’Hépato-gastroentérologie, AP-HP, Hôpital Antoine Béclère, Clamart, France. Faculté de Médecine, Université Paris-Sud/Paris-Saclay, Kremlin-Bicêtre, France. INSERM U996, Clamart, France. [Jacquot E, Deltour N] Pharmacoepidemiology Department, Servier, Suresnes, France; IDIAP Jordi Gol |
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Abstract:
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Acute liver injury; Antidepressants; Case-control |
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Abstract:
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Lesió hepàtica aguda; Antidepressius; Control de casos |
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Abstract:
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Lesión hepática aguda; Antidepresivos; Control de casos |
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Abstract:
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Background
Agomelatine is a melatonin receptor agonist and serotonin 5-HT2C receptor antagonist indicated for depression in adults. Hepatotoxic reactions like acute liver injury (ALI) are an identified risk in the European risk management plan for agomelatine. Hepatotoxic reactions have been reported for other antidepressants, but population studies quantifying these risks are scarce. Antidepressants are widely prescribed, and users often have risk factors for ALI (e.g. metabolic syndrome).
Objective
The goal was to estimate the risk of ALI associated with agomelatine and other antidepressants (fluoxetine, paroxetine, sertraline, escitalopram, mirtazapine, venlafaxine, duloxetine, and amitriptyline) when compared with citalopram in routine clinical practice.
Method
A nested case–control study was conducted using data sources in Denmark, Germany, Spain, and Sweden (study period 2009–2014). Three ALI endpoints were defined using International Classification of Diseases (ICD) codes: primary (specific codes) and secondary (all codes) endpoints used only hospital discharge codes; the tertiary endpoint included both inpatient and outpatient settings (all codes). Validation of endpoints was implemented. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for current use were estimated for each data source and combined.
Results
We evaluated 3,238,495 new antidepressant and 74,440 agomelatine users. For the primary endpoint, the OR for agomelatine versus citalopram was 0.48 (CI 0.13–1.71). Results were also < 1 when no exclusion criteria were applied (OR 0.37; CI 0.19–0.74), when all exclusion criteria except alcohol and drug abuse were applied (OR 0.47; CI 0.20–1.07), and for the secondary (OR 0.40; CI 0.05–3.11) and tertiary (OR 0.79; CI 0.50–1.25) endpoints. Regarding other antidepressants versus citalopram, most OR point estimates were also below one, although with varying widths of the 95% CIs. The result of the tertiary endpoint and the sensitivity analyses of the primary endpoint were the most precise.
Conclusion
In this study, using citalopram as a comparator, agomelatine was not associated with an increased risk of ALI hospitalisation. The results for agomelatine should be interpreted in the context of the European risk minimisation measures in place. Those measures may have induced selective prescribing and could explain the lower risk of ALI for agomelatine when compared with citalopram. Most other antidepressants evaluated had ORs suggesting a lower risk than citalopram, but additional studies are required to confirm or refute these results. |
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Subject(s):
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-Farmacoepidemiologia
-Antidepressius
-Medicaments - Assaigs clínics
-DISCIPLINES AND OCCUPATIONS::Health Occupations::Medicine::Public Health::Epidemiology::Health Occupations::Pharmacoepidemiology
-CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Psychotropic Drugs::Antidepressive Agents
-ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation
-DISCIPLINAS Y OCUPACIONES::profesiones sanitarias::medicina::salud pública::epidemiología::profesiones sanitarias::farmacoepidemiología
-COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos del sistema nervioso central::fármacos psicotrópicos::antidepresivos
-TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas de investigación::estudios de evaluación como asunto::evaluación de medicamentos |
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Rights:
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Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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Document type:
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Article
Article - Published version |
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Published by:
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Adis
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